A llama-derived gelsolin single-domain antibody blocks gelsolin–G-actin interaction

RNA interference has tremendously advanced our understanding of gene function but recent reports have exposed undesirable side-effects. Recombinant Camelid single-domain antibodies (VHHs) provide an attractive means for studying protein function without affecting gene expression. We raised VHHs against gelsolin (GsnVHHs), a multifunctional actin-binding protein that controls cellular actin organization and migration. GsnVHH-induced delocalization of gelsolin to mitochondria or the nucleus in mammalian cells reveals distinct subpopulations including free gelsolin and actin-bound gelsolin complexes. GsnVHH 13 specifically recognizes Ca²⁺-activated gelsolin (K _d ~10 nM) while GsnVHH 11 binds gelsolin irrespective of Ca²⁺ (K _d ~5 nM) but completely blocks its interaction with G-actin. Both GsnVHHs trace gelsolin in membrane ruffles of EGF-stimulated MCF-7 cells and delay cell migration without affecting F-actin severing/capping or actin nucleation activities by gelsolin. We conclude that VHHs represent a potent way of blocking structural proteins and that actin nucleation by gelsolin is more complex than previously anticipated.     

Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity

Multiple organs cooperate to regulate appetite, metabolism, and glucose and fatty acid homeostasis. Here, we identified and characterized lymphatic vasculature dysfunction as a cause of adult-onset obesity. We found that functional inactivation of a single allele of the homeobox gene Prox1 led to adult-onset obesity due to abnormal lymph leakage from mispatterned and ruptured lymphatic vessels. Prox1 heterozygous mice are a new model for adult-onset obesity and lymphatic vascular disease.     

Combining the People Power and the Process Power to Achieve Six Sigma Process Capability——A Case Study

Achieving Six-Sigma process capability starts with l istening to the Voice of the Customers, and it becomes a reality by combining th e People Power and the Process Power of the organisation. This paper presents a Six-Sigma implementation case study carried out in a magnet manufacturing compa ny, which produces bearing magnets to be used in energy meters. If the thickness of the produced bearing magnets is between 2.35 mm and 2.50 mm, they will be ac cepted by the customers. All the time the company coul...     

Linear and nonlinear optical spectroscopy of a strongly coupled microdisk-quantum dot system

Cavity quantum electrodynamics, the study of coherent quantum interactions between the electromagnetic field and matter inside a resonator, has received attention as both a test bed for ideas in quantum mechanics and a building block for applications in the field of quantum information processing. The canonical experimental system studied in the optical domain is a single alkali atom coupled to a high-finesse Fabry-Perot cavity. Progress made in this system has recently been complemented by research involving trapped ions, chip-based microtoroid cavities, integrated microcavity-atom-chips, nanocrystalline quantum dots coupled to microsphere cavities, and semiconductor quantum dots embedded in micropillars, photonic crystals and microdisks. The last system has been of particular interest owing to its relative simplicity and scalability. Here we use a fibre taper waveguide to perform direct optical spectroscopy of a system consisting of a quantum dot embedded in a microdisk. In contrast to earlier work with semiconductor systems, which has focused on photoluminescence measurements, we excite the system through the photonic (light) channel rather than the excitonic (matter) channel. Strong coupling, the regime of coherent quantum interactions, is demonstrated through observation of vacuum Rabi splitting in the transmitted and reflected signals from the cavity. The fibre coupling method also allows us to examine the system's steady-state nonlinear properties, where we see a saturation of the cavity-quantum dot response for less than one intracavity photon. The excitation of the cavity-quantum dot system through a fibre optic waveguide is central to applications such as high-efficiency single photon sources, and to more fundamental studies of the quantum character of the system.     

Studies on thermally grown oxide as an interface between plasma-sprayed coatings and a nickel-based superalloy substrate

A thermally grown oxide layer formed by hot corrosion was investigated as an interface between plasma-sprayed coatings and a nickel-based superalloy substrate. The hot corrosion mechanism of NiCr-Cr₂O₃ and Al₂O₃-40wt% TiO₂ (A40T) plasma coated Inconel 617 was evaluated. The experiments were carried out at 1000℃ using a combination of Na₂SO₄, NaCl, and ₂O₅ salts to simulate the conditions of a gas turbine in a marine environment. The hot corrosion results revealed the spallation and dissolution of oxides upon prolonged exposure. Optical images and scanning electron micrographs of the exposed samples revealed the formation of oxide scale and provided details of its morphology in NiCr-Cr₂O₃ coated samples. Microstructure characterization of A40T coatings demonstrated a thermally grown oxide (TGO) layer at 1000℃. Increasing the thickness of the TGO layer decreased the corrosion resistance. The elemental analysis and image mapping revealed the migration of active elements from the substrate and coatings toward the corrosive environment.     

A blend of small molecules regulates both mating and development in Caenorhabditis elegans

In many organisms, population-density sensing and sexual attraction rely on small-molecule-based signalling systems. In the nematode Caenorhabditis elegans, population density is monitored through specific glycosides of the dideoxysugar ascarylose (the 'ascarosides') that promote entry into an alternative larval stage, the non-feeding and highly persistent dauer stage. In addition, adult C. elegans males are attracted to hermaphrodites by a previously unidentified small-molecule signal. Here we show, by means of combinatorial activity-guided fractionation of the C. elegans metabolome, that the mating signal consists of a synergistic blend of three dauer-inducing ascarosides, which we call ascr#2, ascr#3 and ascr#4. This blend of ascarosides acts as a potent male attractant at very low concentrations, whereas at the higher concentrations required for dauer formation the compounds no longer attract males and instead deter hermaphrodites. The ascarosides ascr#2 and ascr#3 carry different, but overlapping, information, as ascr#3 is more potent as a male attractant than ascr#2, whereas ascr#2 is slightly more potent than ascr#3 in promoting dauer formation. We demonstrate that ascr#2, ascr#3 and ascr#4 are strongly synergistic, and that two types of neuron, the amphid single-ciliated sensory neuron type K (ASK) and the male-specific cephalic companion neuron (CEM), are required for male attraction by ascr#3. On the basis of these results, male attraction and dauer formation in C. elegans appear as alternative behavioural responses to a common set of signalling molecules. The ascaroside signalling system thus connects reproductive and developmental pathways and represents a unique example of structure- and concentration-dependent differential activity of signalling molecules.